Dendritic cell vaccine in addition to FOLFIRI regimen improve antitumor effects through the inhibition of immunosuppressive cells in murine colorectal cancer model

Although chemotherapy is still one of the best treatments for most cancers, immunotherapies such as dendritic cell (DC) vaccines have emerged as an alternative protocol for destroying residual tumors. In this study, we investigated antitumor effects of the combined therapy using DC vaccine and irinotecan plus infusional 5-fluorouracil and leucovorin (FOLFIRI) which have been clinically used for the treatment of colorectal cancer. A maximum tolerated dose of FOLFIRI was preliminarily determined for MC38/CEA2 colorectal cancer model. Vaccination with DC expressing carcinoembryonic antigen (CEA) enhanced antitumor effect after FOLFIRI treatment. The combined therapy also increased CEA-specific Th1 and cytotoxic T-cell responses. Interestingly, although FOLFIRI treatment rather showed a rebound in the number of myeloid-derived suppressor cells (MDSC) and regulatory T-cells (Treg) after 14 days, additional DC vaccine could inhibit the rebound of these immunosuppressive cells. Furthermore, mice cured by the combined therapy showed antigen-specific T-cell responses and resistance against challenge of MC38/CEA2 compared with mice cured with FOLFIRI. These results demonstrated that DC vaccine in addition to FOLFIRI regimen could improve antitumor effects through the inhibition of immunosuppressive tumor environments in murine colorectal cancer model, and may provide knowledge useful for the design of chemo-immunotherapeutic strategies for the treatment of colorectal carcinoma in clinical trials. (C) 2010 Elsevier Ltd. All rights reserved.